PloS one · 2013
A large scale gene-centric association study of lung function in newly-hired female cotton textile workers with endotoxin exposure.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
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Zhang Ruyang, Zhao Yang, Chu Minjie, Mehta Amar, Wei Yongyue, Liu Yao, Xun Pengcheng, Bai Jianling, Yu Hao, Su Li, Zhang Hongxi, Hu Zhibin, Shen Hongbing, Chen Feng, Christiani David C
Аннотация
BACKGROUND: Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood.
OBJECTIVE: We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.
METHODS: DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.
RESULTS: Two SNPs were found to be significant (P<6.29×10(-5)), including rs1910047 (P = 3.07×10(-5), FDR = 0.0778) and rs9469089 (P = 6.19×10(-5), FDR = 0.0967), as well as other eight suggestive (P<5×10(-4)) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (P trend = 3.01×10(-18)). However, the association was different among age subgroups (P = 7.11×10(-6)) and endotoxin subgroups (P = 1.08×10(-2)). Functional network analysis illustrates potential biological connections of all interacted genes.
CONCLUSIONS: Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers.
OBJECTIVE: We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.
METHODS: DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.
RESULTS: Two SNPs were found to be significant (P<6.29×10(-5)), including rs1910047 (P = 3.07×10(-5), FDR = 0.0778) and rs9469089 (P = 6.19×10(-5), FDR = 0.0967), as well as other eight suggestive (P<5×10(-4)) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (P trend = 3.01×10(-18)). However, the association was different among age subgroups (P = 7.11×10(-6)) and endotoxin subgroups (P = 1.08×10(-2)). Functional network analysis illustrates potential biological connections of all interacted genes.
CONCLUSIONS: Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers.
Предметные рубрики MeSH
AdolescentAdultByssinosisEndotoxinsEpistasis, GeneticFemaleForced Expiratory VolumeGene Regulatory NetworksGene-Environment InteractionGenetic Predisposition to DiseaseHumansMiddle AgedOccupational DiseasesOccupational ExposurePolymorphism, Single NucleotideRespiratory Function TestsTextilesYoung Adult